Improving Diagnostic Accuracy for Acute Heart Failure

提高急性心力衰竭的诊断准确性

• 批准号: 10405617
• 负责人: SEAN PATRICK COLLINS
• 金额: $ 135.22万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10405617
• 关键词: Accident and Emergency department; Acute; Address; Affect; American; Antibiotics; Asthma; Biological; Biological Assay; Biological Markers; Bronchodilator Agents; Calibration; Cardiac; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Data; Congestive Heart Failure; Data; Derivation procedure; Diagnosis; Diagnostic tests; Discrimination; Diuretics; Dyspnea; EFRAC; Emergency department visit; Enrollment; Frequencies; Future; Guidelines; Heart failure; Hospitalization; IV Fluid; Investigation; Knowledge; Left Ventricular Ejection Fraction; Logistic Models; Medicare; Modeling; Natriuretic Peptides; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Performance; Plasma; Pneumonia; Probability; Prognosis; Proteins; Proteomics; Recording of previous events; Reporting; Research Design; Sample Size; Sampling; Shortness of Breath; Signs and Symptoms; Specificity; Symptoms; Testing; Thoracic Radiography; Validation; Work; accurate diagnosis; adjudicate; adverse outcome; base; biomarker discovery; biomarker panel; circulating biomarkers; clinical diagnostics; clinical practice; cohort; cost; diagnosis standard; diagnostic accuracy; diagnostic strategy; health care service utilization; improved; mortality; novel; novel diagnostics; novel marker; performance tests; predictive modeling; preservation; prospective; protein biomarkers; recruit; respiratory

PROJECT SUMMARY/ABSTRACT Acute heart failure (HF) is highly morbid, lethal, and costly. It is a difficult diagnosis to make given its symptoms and signs overlap with other cardiac and non-cardiac conditions. In the emergency department (ED), misdiagnosis of acute HF is common and associated with adverse outcomes. Biomarker testing can facilitate accurate diagnosis; however, natriuretic peptides (NP) are the only guideline recommend biomarker of HF for diagnostic testing, and are better for ruling-out, rather than ruling-in, acute HF. Even with NP testing, in contemporary clinical practice misdiagnosis of acute HF still occurs in 10 to 45% of patients presenting to the ED with dyspnea. Clinical prediction models including multiple biomarkers hold promise for improving diagnostic accuracy. The few prior studies investigating a multiple biomarker approach for diagnosing acute HF were limited by constraint to highly correlated markers from known biologic pathways, relatively small sample sizes, lack of inclusion of all a priori selected biomarkers into a single model, and absence of validation cohorts. Our study design addresses these limitations. Recent advances in “omics” enable novel biomarker discovery on a larger scale and investigations less “biased” by existing knowledge. Thus, our overarching hypothesis is a multi-marker model incorporating novel proteins discovered with plasma proteomics improves diagnostic accuracy for acute HF. In preliminary work, we performed a proof of concept study utilizing plasma proteomics to discover a multi-marker panel of 21 biomarkers which improved diagnostic accuracy for acute HF beyond current clinical practice using clinical data and NP levels. Our promising preliminary data motivate broader discovery in a larger sample size with subsequent derivation and validation of a multi-marker model for diagnosing acute HF in independent samples of adequate size. Our specific aims are to: 1) expand the discovery cohort and refine the multi-marker panel of 21 biomarkers to improve diagnostic accuracy for acute HF, 2) derive a model for diagnosing acute HF incorporating the 21-biomarker panel, 3) test performance of the multi-marker model in a prospective validation cohort, and 4) assess the incremental value of the multi- marker model for diagnosing acute HF. In aim 1, existing plasma samples from 989 patients will be used to assay 925 proteins to discover a smaller set of novel biomarkers most strongly associated with an adjudicated acute HF diagnosis. In aim 2, we will utilize an existing prospective observational cohort, EMROC-AHF, to derive the multi-marker model in 1,000 patients who presented to the ED with acute dyspnea. In aim 3, from four EDs in Detroit, MI and Nashville, TN we will prospectively recruit a new sample of 1,000 patients presenting with acute dyspnea and adjudicate the presence of acute HF by cardiologist panel review. In aim 4, we will compare our multi-marker model against the current clinical approach for diagnosing acute HF using the cohorts for Aims 2 and 3. Given the burden of HF, the frequency of inaccurate diagnosis and its adverse consequences, we will address a significant unmet need by improving diagnostic accuracy for acute HF.

项目总结/摘要 急性心力衰竭（HF）是一种高度病态、致命和昂贵的疾病。根据症状很难做出诊断 并且体征与其他心脏和非心脏疾病重叠。在急诊科（艾德）， 急性HF的误诊是常见的，并且与不良结果相关。生物标志物测试可以促进 准确诊断;然而，利钠肽（NP）是HF的唯一指南推荐生物标志物， 诊断测试，并更好地排除，而不是排除，急性HF。即使使用NP测试， 在当代临床实践中，10 - 45%的急性HF患者仍会出现误诊， 艾德伴呼吸困难。包括多种生物标志物的临床预测模型有望改善 诊断准确性。研究多种生物标志物方法诊断急性HF的少数先前研究 受来自已知生物学途径的高度相关标志物的限制，相对较小的样本 尺寸，缺乏将所有先验选择的生物标志物纳入单一模型，以及缺乏验证 同伙我们的研究设计解决了这些局限性。“组学”的最新进展使新的生物标志物成为可能 更大规模的发现和更少受现有知识“偏见”的调查。因此， 假设是一种多标记模型，其结合了血浆蛋白质组学发现的新蛋白质， 急性HF的诊断准确性。在初步工作中，我们利用等离子体进行了概念验证研究 蛋白质组学发现了一个由21种生物标志物组成的多标志物组，提高了急性胰腺炎的诊断准确性。 使用临床数据和NP水平，HF超出当前临床实践。我们有希望的初步数据 在更大的样本量中进行更广泛的发现，随后推导并验证多标记模型， 在足够大小的独立样本中诊断急性HF。我们的具体目标是：1）扩大 发现队列，并完善21种生物标志物的多标志物组，以提高急性 HF，2）推导出用于诊断急性HF的模型，该模型结合了21种生物标志物组，3）测试 前瞻性验证队列中的多标志物模型，以及4）评估多标志物模型的增量值。 用于诊断急性HF的标记物模型。在目标1中，来自989名患者的现有血浆样本将用于 测定925种蛋白质，以发现与裁定的 急性HF诊断。在目标2中，我们将利用现有的前瞻性观察队列EMROC-AHF， 在1,000名因急性呼吸困难就诊于艾德的患者中推导出多标志物模型。在目标3中， 在密歇根州底特律和田纳西州纳什维尔的四个急诊室，我们将前瞻性招募1,000名患者的新样本 出现急性呼吸困难，并由心脏病专家小组审查判定是否存在急性HF。在目标4中， 我们将比较我们的多标志物模型与目前诊断急性HF的临床方法， 目标2和目标3的队列。考虑到HF的负担，不准确诊断的频率及其不良反应， 因此，我们将通过提高急性HF的诊断准确性来解决一个重大的未满足的需求。